In the treatment of diseases or ailments of the colon or rectum administration of the pharmacologically active agent to the affected site may be required. Orally administrable pharmaceutical compositions however have frequently been found ineffective in this respect as a result of the absorption of the pharmacologically active agent in the digestive tract before the colon or rectum is reached. Consequently, the delivery of pharmacologically active agents to the colon or rectum has conventionally been achieved by rectal administration, by the use of either suppositories, aerosols, or enemas. However, rectal administration generally is less convenient and less acceptable to a patient than oral administration. Further, said rectal administration is not suitable for treating the right side of the colon. In particular, suppositories are only effective for the rectum and enemas rarely reach beyond the left side of the colon.
Several “delayed-release” forms of orally administrable pharmaceuticals have been proposed. UK Patent No. 1219026 describes to a method to embed individual particles of a pharmacologically active agent in a slowly-disintegrating or slowly-dissolving resin having a particular dissolution profile to provide an orally administrable pharmaceutical composition for selectively administering the agent to the large intestine. The resin is selected such that the agent remains substantially protected by the resin while the particles travel through the stomach and small intestines of a patient and that the agent is substantially completely exposed at the time the particles reach the large intestine.
UK Patent No. 2021409 describes sustained or controlled release compositions containing 5-aminosalicylic acid in the form of particles or granules which are coated with a slowly soluble or digestible or semi-permeable layer of material, such as beeswax, carnauba wax, stearic or palmitic acids or cetyl alcohol. Reference also is made to coating tablets of the coated or uncoated 5-aminosalicylic acid with a continuous film of a material, such as shellac or cellulose acetate phthalate, which is resistant and impermeable to gastric secretions but susceptible to intestinal secretions.
International Patent Application WO 81/02671 describes sustained-release tablets prepared from granules containing 5-aminosalicylic acid which are coated with a cellulose derivative, such as ethyl cellulose.
European Patent Application No. 40590A describes a method for coating a core of 5-aminosalicylic acid with a coating material comprising at least: (a) 10-85% by weight of an anionic carboxylic polymer soluble only above pH 5.5; and (b) 15-90% by weight of a water-soluble, quaternary ammonium substituted acrylic polymer. It is stated that the coating normally will be 3-60 microns, preferably 10-30 microns thick and that partly methyl esterified methacrylic acid polymers are suitable anionic carboxylic polymers for use as component (a). In the Examples, Eudragit® L and a mixture of Eudragit® L and Eudragit® S constitute the component (a) and in all cases the coatings dissolved at below pH 7.
U.S. Pat. No. 5,541,170 describes an orally administrable pharmaceutical composition for selectively administering 5-aminosalicylic acid, or pharmaceutically acceptable salt or ester thereof, to the large intestine, comprising a solid oral dosage form containing a pharmaceutically effective amount for the treatment of ulcerative colitis or Crohn's disease of the colon of said 5-aminosalicylic acid, salt or ester, said solid oral dosage form being coated with a layer which is insoluble in gastric juice and in intestinal juice below pH 7, but soluble in colonic intestinal juice, whereby the dosage form releases the 5-aminosalicylic acid, salt or ester to the right side of the colon.
U.S. Pat. No. 5,541,171 describes a non-sustained release orally administrable pharmaceutical composition for selectively administering 5-aminosalicylic acid or a pharmaceutically acceptable salt or ester thereof to the large intestine, the composition comprising a solid oral dosage form containing a pharmaceutically effective amount for the treatment of ulcerative colitis or Crohn's disease of said 5-aminosalicylic acid, ester or salt and said oral dosage form is coated with a 60-150 micron thick layer of an anionic co-polymer of methacrylic acid and methacrylic acid methyl ester in which the ratio of free carboxyl groups to ester groups is about 1:2 and which is insoluble in gastric juice and in intestinal juice below pH 7, but soluble in colonic intestinal juice, whereby the oral dosage form remains intact until it reaches the colon and releases 5-aminosalicylic acid to the right side of the colon.